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The University of Southampton
Institute for Life Sciences


Regulation of Gene Expression and Development

Translational control mechanisms (Dr Mark Coldwell)

Central to translation initiation (the start of protein synthesis) is the selection of the initiation codon, which is usually an AUG, although a growing number of mRNAs have been found to use non-canonical near-cognate initiation codons e.g. CUG, GUG, UUG. Dr Coldwell and colleagues are investigating the usage and regulation of these alternative initiation codons in order to examine the importance of alternative initiation codon selection in the generation of protein isoform diversity, a previously neglected aspect of gene expression. This work will modify and extend our understanding of the protein-coding potential of all eukaryotic genomes, as the underlying mechanisms of translational control are conserved across species.

Selection of the correct initiation codon is mediated by several initiation factors, and part of this project explores the regulation of AUG usage versus non-AUG initiation codons. It is clear that the selection of certain initiation codons may have beneficial or detrimental effects on the cell and it is important to establish in which stages of cell growth and/or disease progression that this form of translational control occurs. Deregulation of the appropriate selection of translation initiation codons may be important in the status of certain diseases, including cancer.

Research Projects

Mechanisms of alternative translation initiation codon selection in the regulation of eukaryotic gene expression - In a growing number of cases, initiation codons other than the canonical AUG triplet are used to initiate translation. We are investigating how widespread this phenomenon is, and what it means for current models of initiation.

Transcriptome-wide prediction of eukaryotic translation initiation - Combining bioinformatics searches with experimental data to broaden our knowledge of eukaryotic translation initiation.

Characterisation of BAG-1 as a therapeutic target in HER2 positive breast cancer - Working with colleagues in Medicine, this project aims to decipher the molecular mechanism for changes in BAG-1 expression HER2+ breast cancer.

Developmental Biology (Dr Claire Clarkin)

Dr Clarkin’s research is focussed on how blood vessels interact with tissues and organs during development, adulthood and disease. Specifically, she is interested in how tissue derived factors such as Vascular Endothelial Growth Factor or Transforming Growth Factor β can modulate endothelial cell behaviour and Dr Clarkin has unique models in place to modulate the expression levels of such genes in vitro and in vivo. Examples of projects she is involved in include i) study of endothelial cell interactions in bone, during remodelling, osteoporosis and following orthopaedic surgery and ii) targeting the blood supply in of islets of Langerhans to increase islet transplantation success, a current treatment for Type 1 Diabetes.

Research Projects

Modulating Vascular Endothelial Growth Factor gene expression in bone - working with colleagues in Engineering and Harvard University to identify new drug targets that will permit selective control of bone's bloold supply to allow sufficient support for the process of bone renewal.

Improving islet endothelial cell viability to improve islet transplantation success - aims to identify mechanisms which drive islet endothelial cell loss prior to and during islet graft translation.

Tissue specific endothelial and mesenchymal stem cell interactions - investigating mechanisms and the impact on procedures use of MSC's such as tissue translation and regeneration.

FioNA webpages

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Related Staff Member

Related Staff Member

Academic Contacts:

Transcription initiation:

Dr Jeremy Blaydes

Dr Emre Sayan

Dr Jonathan Strefford

Prof Keith Fox

Dr Judith Eckert

Prof Tom Fleming


Michela Raponi

Dr Diana Baralle

Dr Claire Clarkin


Dr Tilman Sanchez-Elsner

Prof John Holloway

Post-translational modifications

Prof Chris Proud

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